Analysis of Vestibular Compensation Following Clinical Intervention for Vestibular Schwannoma

Migraine Clinical Trial

Official title:

Temporal Synthesis of Vestibular and Extra-Vestibular Sensory Signals

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04196933
• Other study ID #: 2018P003117
• Secondary ID: 1R01DC017425-01
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 5, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: Massachusetts Eye and Ear Infirmary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multiple sensory cues are typically generated by discrete events, and while they do not reach the cerebrum simultaneously, the brain can bind them temporally if they are interpreted as corresponding to a single event. The temporal binding of vestibular and non-vestibular sensory cues is poorly understood and has not been studied in detail, despite the fact that the vestibular system operates in an inherently multimodal environment. In this study, the researchers are investigating the physiology and pathophysiology of vestibular temporal binding by studying normal subjects, patients with peripheral and central vestibular dysfunction, and patients with vestibular and cochlear signals provided by prosthetic implants in the inner ear.

Description:

Multiple sensory cues are generated by discrete events (e.g., the vestibular-visual signals after hitting a pothole) and while they do not reach the cerebrum simultaneously, the brain can synthesize them if they are interpreted as corresponding to a single event. This is critical because the central representation of an event is improved if two or more relevant cues are integrated but conversely is degraded if unrelated inputs are synthesized. Little research has focused on temporal binding of vestibular signals with other sensory cues, even though the vestibular system operates in an inherently multimodal environment, and virtually nothing is known about temporal binding abnormalities in patients with peripheral or central vestibular disorders. The investigators will use psychophysical tests (quantifying the PSS [point of subjective simultaneity] and TBW [temporal binding window]) to study vestibular temporal binding in normal people, patients with combined vestibular and cochlear prostheses, and patients with peripheral or central vestibular dysfunction. The researchers will investigate two fundamental aspects of temporal binding: its dependence on signal precision and adaptation driven by habitual exposure to sensory patterns. Furthermore, the researchers will investigate how and why temporal binding differs from normal in patients with peripheral and central vestibular dysfunction.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 472
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 80 Years

Eligibility

Inclusion Criteria:

Normal subjects

• normal vestibular-oculomotor exams

• normal low-frequency standard rotational testing

• normal hearing

Migraine

• meets International Headache Society (IHS) criteria for migraine with or without aura

• tested more than 2 weeks after most recent migraine headache

Vestibular Migraine

• meets Barany Society criteria for vestibular migraine, which includes:

• episodic vestibular symptoms that occur with headaches that meet the IHS criteria for migraine

• tested more than 2 weeks after most recent migraine headache or vestibular episode

Vestibular Schwannoma

• existence of unilateral vestibular schwannoma (pre & post clinical intervention e.g. surgical resection)

• must plan to have clinical intervention such as sub-occipital surgical approach with complete sectioning of the vestibular nerve

• rotational testing to assess pre-surgical vestibular function

• audiogram

• brain MRI consistent with vestibular schwannoma

• audiography in each ear

Vestibular (VI) and Cochlear (CI) Implant subjects

• scheduled for CI surgery because of deafness

• minimum 5 year history of documented absence of auditory and vestibular function, based on review of their audiograms and vestibular tests

• specific vestibular criteria: peak ice water caloric response of less than 3deg/s for each ear; yaw VOR time constant <3s and gain <0.25; and reduced head impulse gain (<0.25) for all canal planes

• specific audiographic criteria: 80dB or greater sensorineural hearing loss in both ears

Exclusion Criteria:

Normal subjects

• history of otologic or neurologic disease

• on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

• pregnant or recently (<6mos) pregnant

Migraine

• history of vestibular symptoms (other than motion sickness)

• evidence of other neurologic or otologic dysfunction

• on migraine prophylactic medications

• on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Vestibular Migraine (VM)

• other neurologic or otologic dysfunction as defined above except for central eye movement findings that are consistent with VM and therefore not exclusionary.

• on migraine prophylactic medication

• on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Vestibular Schwannoma

• other otologic disease (other than presbycusis) or any neurologic disease (other than migraine)

• on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Related Conditions & MeSH terms

• Dizziness
• Migraine
• Migraine Disorders
• Motion Sickness
• Neurilemmoma
• Neuroma, Acoustic
• Vertigo
• Vestibular Diseases
• Vestibular Disorder
• Vestibular Migraine
• Vestibular Schwannoma

Intervention

Behavioral:
• Temporal Binding Adaptation - TBW training
The investigators will use a temporal order judgment (TOJ) with a visual (light) cue and a motion (yaw rotation, y-translation) cue. The relative timing of the motion onset and the light are varied and subjects indicate which occurred first by pressing a button after the motion ends. The TOJ task will generate a psychometric curve and the PSS (point of subjective simultaneity) and TBW (temporal binding window) are calculated. Then training focuses on SOAs (stimulus onset asynchronies) near the TBW borders (e.g., PSS +/- 0.5xTBW), starting from 50 ms outside the TBW and moving randomly towards the PSS. The goal of the training is to narrow the TBW -- training trials will be provided for 30 min and after each response the subject is told if their response was right or wrong. After training, the TOJ task is repeated to determine how the TBW has changed. Sham training will be the same as the actual training except that verbal feedback of response accuracy will not be provided.
• Temporal Binding Adaptation - PSS training
After the PSS and TBW are calculated with the standard TOJ paradigm, 100 training trials are provided where the SOA is set to [PSS - 200 ms], with the goal of shifting the PSS more negative. Then the TOJ task will be repeated but every 10 testing trials will be followed by 10 training trials (SOA = PSS - 200), and this pattern will be repeated 10 times to 100 more training trials interspersed with the Post TOJ data. Subjects will respond after all trials and testing and training will not be distinguished. After this is completed, the new PSS and TBW are calculated. Sham PSS training will be identical to the above except that the 'training' period will consist of random SOAs rather than a series of fixed SOAs.
• Temporal Binding Adaptation - PSS adaptation with VI stimulation
The adaptation will utilize the same approach used in non-implanted patients. The investigators will provide a repeated, fixed SOA with either the CI or VI leading the other stimulus by 220 ms. After the training period, which will match the number of stimuli pairs provided to our normal vestibular-auditory control subjects undergoing PSS adaptation, the TOJ study is repeated to recalculate the PSS and TBW.
• Chronic Motion-modulated Stimulation
To provide 8 hours of 'physiologic' CI and VI inputs during normal activities, the investigators will employ standard motion-modulated stimulation with the VI. This requires pre-adaptation to a 200 pps tonic stimulation rate (to emulate the push-pull design of the native vestibular system allowing modulating stimulation upward or downward with opposite directions of motion). The three electrodes are connected to the head-mounted prosthetic circuit, which consists of three angular velocity sensors (one aligned with the sensitive axis of each canal) such that head rotations in the plane of the given canal modulate the stimulation rate of the corresponding electrode, upward (for ipsi) or downward (for contralateral) head rotations, thereby simulating normal canal-mediated modulations.

Locations

Country	Name	City	State
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts Eye and Ear Infirmary	National Institute on Deafness and Other Communication Disorders (NIDCD), Oregon Health and Science University, University of Geneva, Switzerland

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in postural sway/balance	Measurements of postural sway during Romberg testing on floor and foam (including an extra 60s balance test during which subject stands on foam and shakes head left and right at 1hz frequency while fixating on a point a set distance away) pre & post temporal binding adaptation (TBW & PSS training).	baseline and post temporal binding adaptation (1 hour)
Primary	Change in rapid measure of gait	This measure is scored before and after PSS and TBW adaptation in UVD (unilateral vestibular dysfunction) patients. Gait is scored by performance on a task derived from the FGA (walking 40 feet while turning the head from side to side). It is scored on a 0 to 10 visual scale and provides a rapid assessment of vestibular function pre and post adaptation.	baseline and post temporal binding adaptation (1 hour)
Primary	Change in measure of inducible dizziness	Looking at the change between before and after PSS and TBW adaptation in UVD (unilateral vestibular dysfunction) patients. Inducible dizziness is the symptom severity provoked by a task derived from the FGA (walking 40 feet while turning the head from side to side). It is scored on a 0 to 10 visual scale and provides a rapid assessment of vestibular function pre and post adaptation.	baseline and post temporal binding adaptation (1 hour)
Primary	Change in Motion Sickness (MS) Susceptibility	The investigators will use a well-validated variant of the classic Coriolis task, a pseudo-Coriolis task where subjects view a strong yaw-axis OKN stimulus while the head is tilted passively in roll at 1.0 Hz (starting 5 s after the vection illusion begins). The investigators found empirically that 40 roll tilts of the head were adequate to induce a range of MS symptoms, from virtually none in people with minimal MS sensitivity to severe nausea in people with more prominent MS sensitivity. Subjects grade their MS symptoms before and after the pseudo-Coriolis task using a simple visual analog (0 to 10) scale.	baseline and post temporal binding adaptation (1 hour)
Primary	Change in Point of Subjective Simultaneity (PSS)	Pre and post chronic motion-modulated stimulation in CI/VI patients - the PSS will be measured during temporal binding testing	baseline and 1 hour post 8-hour VI-CI 'physiologic' stimulation